Differential Requirements for DOCK2 and phosphoinositide-3-kinase Gamma During T and B Lymphocyte Homing

Immunity. 2004 Sep;21(3):429-41. doi: 10.1016/j.immuni.2004.07.012.

Abstract

Chemokines guide lymphocytes from blood to secondary lymphoid organs by triggering integrin-dependent firm adhesion under vascular flow and directed migration of T and B lymphocytes within lymphoid tissue. Here, we analyze the roles of DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, and phosphoinositide-3-kinase (PI3K) during lymphocyte recirculation. DOCK2 mediated efficient lymphocyte migration in a largely PI3K-independent manner, although a minor, PI3K-dependent pathway for migration was observed in wild-type and DOCK2-deficient lymphocytes. In T cells, this residual migration depended mainly on PI3Kgamma, whereas other PI3K isoforms were implicated in B cells. In vitro adhesion assays and intravital microscopy of lymphoid organ vasculature uncovered an unexpected defect in integrin activation in DOCK2-/- B cells, whereas lack of DOCK2 did not affect chemokine-triggered integrin activation in T cells. DOCK2 and PI3Kgamma thus play distinct roles during T and B cell integrin activation and migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Adhesion / immunology
  • Cell Movement / immunology*
  • Cells, Cultured
  • Fluorescent Antibody Technique
  • GTPase-Activating Proteins / immunology*
  • GTPase-Activating Proteins / metabolism
  • Immunoblotting
  • Immunohistochemistry
  • Integrins / metabolism
  • Lymphocyte Activation / immunology
  • Lymphoid Tissue / immunology
  • Mice
  • Phosphatidylinositol 3-Kinases / immunology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Actins
  • DOCK2 protein, mouse
  • GTPase-Activating Proteins
  • Integrins
  • Phosphatidylinositol 3-Kinases